It is the aim of the present grant to employ the modern methods of molecular biology to further our understanding in two basic areas of viral oncology. One is to provide information on how viral genes are integrated, maintained and regulated in the course of oncogenic transformation. The other is to delineate the chemical mechanism involved in the polymerization reaction of the reverse transcriptase. It is proposed to examine the question of the integration of viral information and related issues with the aid of the thymidine kinase gene (tk) of the herpesvirus. We have recently successfully isolated the tk gene and demonstrated its transfectability to tk- cells. This system should make possible the ready performance of experiments designed to answer many of the questions on the central and function of viral genes resident in eucaryotic genomes. Our recent discovery of the conditions required by purified reverse transcriptase to produce the DNA complement of the completely sequenced replicating MDV-1 RNA means that much of the accumulated powerful technology of the Q beta replicase system can be applied to the study of the reverse transcriptase reaction. A novel opportunity is provided for an informative analysis of reverse transcription and should yield an understanding of the relation between secondary structure and the polymerization process along with a more satisfying understanding of the chemistry involved.